Physiology and Pharmacology

Nader G. Abraham, Dr. HC, Ph.D., FAHA

Professor and Chairman

Phone:  419-383-4144
Fax:  419-383-2871

E-mail: Nader.Abraham@utoledo.edu 

Education

  • Ph.D.: Biomedical Sciences, Mt. Sinai School of Medicine, New York, 1972-1975  
  • Post Doctoral: Pharmacology/Metabolism, the Rockefeller University, New York, 1975-1976
  • Honorary Doctorate (DR.H.C.) in Pharmacy: University of Catania, Sicily, Italy, 2009

Appointments

2009 - Present Professor and Chairman of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio
   
1993 - Present Visiting and Adjunct Professor, The Rockefeller University, New York
   
2008 - Present Visiting Professor, School of Pharmacy, University of Catania, Italy
   
2009 - Present Adjunct Professor of Pharmacology/Medicine, New York Medical College, New York
   
1996 - 2009 Professor of Pharmacology and Director of Stem Cells & Gene Therapy, New York Medical College, Valhalla, New York
   
1993 - 1996 Professor, Department of Medicine, NYU School of Medicine, New York, New York
   
1978 - 1993 Assistant/Associate/Professor, Department of Medicine, NYMC, Valhalla, New York
   
1977 - 1978

Associate Scientist, Department of Medicine, NYU Medical Center, New York, New York

Research Interests

Research programs in Dr. Abraham’s laboratory are focused on vascular dysfunctions which are a prelude to cardiovascular and metabolic diseases including hypertension, stroke, diabetes and obesity, the role of oxidative stress, inflammatory cytokines, hypoadiponectinemia and lipid-derived from arachidonic acid in the initiation of vascular dysfunction. The central hypothesis focuses on heme oxygenase (the most potent anti-oxidant gene in the human body)-adiponectin-EET that plays an essential role in vascular function. We believe that heme oxygenase acts as a molecular "switch" to genetically reprogram the vascular endothelium through activation of a unique signaling cascade with amplification of protective circuits to provide resistance to vascular dysfunction. Heme oxygenase also serves as the mediator of cross-talk between adipose tissue and the vasculature.  Studies in his lab focus on the impact of adipocyte dysfunction on vascular endothelial integrity through the prism of heme oxygenase.

Human biological materials and experimental animal models of diabetes and obesity are used to examine the use of molecular, gene therapy and stem cell interventions that amplify the heme oxygenase system. Additionally, one of our research approaches represents a powerful tool to identify therapeutic strategies and novel biomarkers for cardiovascular and metabolic diseases (e.g. circulating endothelial cells and progenitor stem cells [EPCs] for better prognosis).  We believe that the effect of anti-diabetic drugs alone or in combination with the antioxidant genes, have a differential impact on stem cell function and vascular diseases as well as on stem cells differentiation into adipocytes and osteoblasts.  The genomic approach and gene array analysis described in these studies represents a powerful tool to systematically investigate therapeutic approaches, and hence, facilitate translational research in hypertension, diabetes and the metabolic syndrome.  Additionally, his lab is developing genetic testing for several human genetic diseases to predict future pathphysiological conditions using cell therapy for disease prevention.

Opportunity for Students

The future is here.  Students are encouraged to spend time (1-3 month election) in my lab as many others have done before.  My students learn both the literature and contribute to it under my mentorship.

Representative Publications

  • Burgess A, Vanella L, Bellner L, Schwartzman ML, Abraham NG. (2011)  Epoxyeicosatrienoic acids and heme oxygenase-1 interaction attenuates diabetes and metabolic syndrome complications.  Prostaglandins Other Lip Mediat.  2011 Nov 15 [Epub ahead of print].
  • Vanella L, Kim DH, Sodhi K, Barbagallo I, Burgess AP, Falck JR, Schwartzman ML, Abraham NG.  (2011)  Crosstalk between EET and HO-1 downregulates Bach1 and adipogenic marker expression in mesenchymal stem cell derived adipocytes. Prostaglandins Other Lip Mediat. 96(1-4):54-62.  Epub 2011 July 27.
  • Vanella L, Di Giacomo C, Acquaviva R, Santangelo R, Cardile V, Barbagallo I, Abraham NG, Sorrenti V. (2011)  The DDAH/NOS pathway in human prostatic cancer cell lines: antiangiogenic effect of L-NAME.  Int J Oncol.  39(5): 1303-10. 
  • Vecoli C, Cao J, Neglia D, Inoue K, Sodhi K, Vanella L, Gabrielson KK, Bedja D, Paolocci N, L'abbate A, Abraham NG.  (2011)  Apolipoprotein A-1 mimetic peptide L-4F prevents myocardial and coronary dysfunction in diabetic mice.  J Cell Biochem.  112(9):2616-2626.
  • Burgess A, Li M, Vanella L, Kim DH, rezzani R, Rodella L, Sodhi K, Canestrar M, Martasek P, Peterson SJ, Kappas A, Abraham NG.  (2010) Adipocyte heme oxygenase-1 induction attenuates metabolic syndrome in both male and female obese mice.  Hypertension. 56-(6):1124-1130.
  • Sodhi K, Inoue K, Gotlinger GH, Canestraro M, Vanella L, Kim DH, Manthati VL, Koduru SR, Falck JR, Schwartzman ML, Abraham NGEpoxyeicosatrienoic Acid Agonist Rescues the Metabolic Syndrome Phenotype of HO-2-Null Mice.  J Pharmacol Exp Ther Dec;331(3);906-916, 2009. 
  • Peterson SJ, Kim DH, Li M, Positano V, Vanella L, Rodella LF, Piccolomini F, Puri N, Gastaldelli A, Kusmic C, L'Abbate A, Abraham NG.  (2009)  The L-4F mimetic peptide prevents insulin resistance through increased levels of HO-1, pAMPK, and pAKT in obese mice.  J Lipid Res. Jul;50 (7): 1293-1304. Epub Feb 17.
  • Li M, Kim DH, Tsenovoy PL, Peterson SJ, Rezzani R, Rodella LF, Aronow WS, Ikehara S, Abraham NG.  (2008)  Treatment of obese diabetic mice with a heme oxygenase inducer reduces visceral and subcutaneous adiposity, increases adiponectin levels, and improves insulin sensitivity and glucose tolerance.  Diabetes Jun; 57(6): 1526-1535. Epub Mar 28.
  • Petrini M, Pacini S, Trombi L, Fazzi R, Montali M, Ikehara S, Abraham NG.  (2009)  Identification and purification of mesodermal progenitor cells from human adult bone marrow.  Stem Cells Dev. Jul-Aug; 18(6): 857-866.
  • Nicolai A, Li M, Kim DH, Peterson SJ, Vanella L, Positano V, Gastaldelli A, Rezzani R, Rodella LF, Drummond G, Kusmic C, L'Abbate A, Kappas A, Abraham NG.  (2009)  Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats.  Hypertension Mar; 53(3): 508-515. Epub Jan 26.
  • Sambuceti G, Morbelli S, Vanella L, Kusmic C, Marini C, Massollo M, Augeri C, Corselli M, Ghersi C, Chiavarina B, Rodella LF, L'Abbate A, Drummond G, Abraham NG, Frassoni F.  (2009)  Diabetes impairs the vascular recruitment of normal stem cells by oxidant damage, reversed by increases in pAMPK, heme oxygenase-1, and adiponectin.  Stem Cells. Feb; 27(2): 399-407.
  • Vanella L, Kim DH, Asprinio D, Peterson SJ, Barbagallo I, Vanella A, Goldstein DS, Ikehara S, Abraham NG.  (2009)  HO-1 expression increases mesenchymal stem cell-derived osteoblast and decrease adipocyte lineages. Bone Novenber 2009.
  • Abraham NG.  Gene targeting and heme oxygenase-1 expression in prevention of hypertension induced by angiotensin II.  (2008)  Hypertension Oct; 52(4): 618-620. Epub 2008 Aug 11.
  • Peterson SJ, Drummond G, Kim DH, Li M, Kruger AL, Ikehara S, Abraham NG.  (2008) L-4F treatment reduces adiposity, increases adiponectin levels, and improves insulin sensitivity in obese mice.  J Lipid Res. Aug;49 (8): 1658-1669. Epub Apr 19.
  • Kim DH, Burgess AP, Li M, Tsenovoy PL, Addabbo F, McClung JA, Puri N, Abraham NG.  (2008)  Heme oxygenase-mediated increases in adiponectin decrease fat content and inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 in Zucker rats and reduce adipogenesis in human mesenchymal stem cells.  J Pharmacol Exp Ther. Jun;325 (3): 833-840. Epub Mar 11.
  • Abraham NG and Kappas A (2008). Pharmacological and Clinical Aspects of Heme Oxygenase.  Pharmacological Reviews 60(1): 79-127.  The most cited and visited pharmacological paper in 2009 (Thomas Reuters).
  • Abraham NG, Li M, Vanella L, Peterson SJ, Ikehara S, Asprinio D.  (2008)  Bone marrow stem cell transplant into intra-bone cavity prevents type 2 diabetes: role of heme oxygenase-adiponectin.  J Autoimmun. May; 30(3): 128-135.
  • L'Abbate A, Neglia D, Vecoli C, Novelli M, Ottaviano V, Baldi S, Barsacchi R, Paolicchi A, Masiello P, Drummond GS, McClung JA, Abraham NG (2007) Beneficial effect of heme oxygenase-1 expression on myocardial ischemia-reperfusion involves an increase in adiponectin in mildly diabetic rats. Am J Physiol Heart Circ Physiol. 293 (6): H3532-H3541.
  • Asija A, Peterson SJ, Stec DE, Abraham NG (2007) Targeting Endothelial Cells with Heme Oxygenase-1 Gene Using VE-Cadherin Promoter Attenuates Hyperglycemia-Mediated Cell Injury and Apoptosis. Antioxid Redox Signal. 9(12): 2065-2074.
  • Abraham NG (2007) Long-term treatment with the apolipoprotein mimetic peptide D-4F increases antioxidants and vascular repair in Type I diabetic rats. J Pharmacol Exp Ther. 322(2): 514-520.
  • Kruger AL, Peterson S, Turkseven S, Kaminski PM, Zhang, Quan S, Wolin MS, Abraham NG (2005) D-4F induces heme oxygenase-1 and extracellular superoxide dismutase, decreases endothelial cell sloughing and improves vascular reactivity in a rat model of diabetes. Circulation14; 111(23): 3126-3134.
  • Abraham NG, Kappas A. (2005) Heme oxygenase and the cardiovascular-renal system. Free Radic Biol Med. 39:1-25. Free Radical Biology & Medicine Top most cited papers 2005 - 2007 Award”.
  • Abraham NG, Kushida T, McClung J, Quan S, Kafaro R, Darzynkiewicz Z, and Wolin MS. (2003) Heme oxygenase-1 attentuates glucose mediated cell growth arrest and apoptosis in human microvessel endothelial cells. Circ Res. 93: 131-139.
  • Botros FT, Laniado-Schwartzman M, Abraham NG. (2002) Regulation of cyclooxygenase- and cytochrome P450-derived eicosanoids by heme oxygenase in the rat kidney. Hypertension 39: 190-197.
  • Abraham NG, Jiang S, Yang L, Zand BA, Laniado-Schwartzman M, Marji J, Drummond, GS, Kappas A. (2000) Adenoviral vector-mediated transfer of human heme oxygenase in rats decreases renal heme-dependent arachidonic acid epoxygenase activity. J Pharm Exp Ther. 293: 494-500.
  • Kaide J-I, Zhang F, Wei Y, Jiang H, Yu C, Wang W-H, Balazy M, Abraham NG, Nasjletti A. (2001) Carbon monoxide of vascular origin attenuates the sensitivity of renal arterial vessels to vasoconstrictors. J Clin Invest. 107: 1163-1171.
  • Feldman E, Ahmed T, Lutton JD, Farley T, Tani K, Freund F Asano, S, Abraham NG. (1997)  Adenovirus mediated alpha interferon (IFN-alpha) gene transfer into CD34+ cells and CML mononuclear cells.  Stem Cells 15: 386-395.
  • Abraham NG, Lavrovsky Y, Schwartzman ML, Stoltz RA, Levere RD, Gerritsen, E., Shibahara, S. and Kappas, A. (1995) Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: Protective effect against heme and hemoglobin toxicity. Proc Natl Acad Sci USA. 92: 6798-6802.
  • da Silva, J-L, Park E, Tiefenthaler M, Escalante B, Schwartzman, ML, Abraham NG. (1994) Tin-mediated heme oxygenase gene activation and cytochrome P450 arachidonate hydroxylase inhibition in spontaneously hypertensive rats. Am J Med Sci. 307: 173-181. Tinsley Harrison Award for the best single cardiology manuscript published by the AJMS.
  • Abraham NG, Lavrovsky Y, Harrison JS, Staudinger R. (1993) Transcriptional modulation of heme oxygenase expression in bone marrow stroma. Blood 82(10):19a.
  • Chertkov JL, Jiang S, Lutton JD, Harrison J, Preti R, Levere RD, Abraham NG. (1993) The hematopoietic stromal microenvironment promotes retrovirus-mediated gene transfer into hematopoietic stem cells. Stem Cells 11: 161-175.
  • Abraham NG, Benz EJ, Karlsson S, Lutton JD, Clark SC. (1992) The stem-cell mavens had a blast – review of the Second International Symposium on Molecular Biology of Hematopoiesis. The New Biologist 4(1): 1-4.
  • Abraham NG, Feldman E, Falck, JR, Lutton JD, Laniado Schwartzman ML. (1991) Modulation of erythropoiesis by novel human bone marrow cytochrome P450-dependent metabolites of arachidonic acid. Blood 78: 1461-1466.
  • Levere RD, Gong Y-F, Kappas A, Bucher DJ, Wormser GP, Abraham NG. (1991) Heme inhibits HIV-1 replication in cell cultures and enhances the anti-viral effect of zidovudine. Proc Natl Acad Sci USA. 88: 1756-1759.
  • Levere RD, Martasek P, Escalante B, Schwartzman ML, Abraham NG. (1990) Effect of heme arginate administration on blood pressure in spontaneous hypertensive rats. J Clin Invest. 86: 213-219.
  • Schwartzman ML, Martasek P, Rios AR, Levere RD, Solangi K, Goodman AI, Abraham NG. (1990) Cytochrome P450-dependent arachidonic acid metabolism in human kidney. Kid Int. 37: 94-99.
  • Sacerdoti D, Escalante B, Abraham NG, McGiff JC, Levere RD, Schwartzman ML. (1989) Treatment with tin prevents the development of hypertension in spontaneously hypertensive rats. Science 243: 388-390.
  • Schwartzman ML, Davis K, McGiff JC, Levere RD, Abraham NG. (1988) Purification and characterization of cytochrome P450-dependent arachidonic acid epoxygenase from human liver. J. Biol. Chem. 263: 2536-2542.
  • Levere RD, Abraham NG. (1982) The bone marrow as a metabolic organ. Amer J Med. 73: 615-616.
Last Updated: 6/26/15